Neuro-imaging applications in Psychiatry Professor David Wyper Institute of Neurological Sciences Glasgow d.wyper@udcf.gla.ac.uk

X-ray Computed Tomography

X-ray Computed Tomography Transmission tomography Developed at EMI laboratories in 1972 by Godfrey Houndsfield

CT in psychiatry Dementia Control Alzheimer’s Hippocampal atrophy

Magnetic Resonance Imaging

Magnetic resonance imaging MRI imaging MRA angiography MRS spectroscopy fMRI functional DTI diffusion tensor

Absorbing RF energy

Emitting RF energy

Tissue contrast MRI ‘pulse sequences’ control the transmission of radio signals and the timing of detection of signals emitted from the body.

Magnetic Resonance Imaging MRI can image structures with detail of 0.1mm. MRI can be repeated without limit. MRI has an enormous impact on clinical in-vivo research

MR in psychiatry Alzheimer’s disease - progression Normal ageing difference at 12m Early onset AD difference at 12m

CSF volume in Schizophrenia Control Schizophrenia

Reduction in gray matter in schizophrenia McIntosh AM….Lawrie SM and Johnstone EC Voxel-based Morphometry of Patients with Schizophrenia or Bipolar Disorder and their Unaffected Relatives, Biol Psychiatry 2004;56:544-552

MR in psychiatry Schizophrenia - activation; Diffusion imaging

Functional MRI In response to a local increase in neuronal firing there is an increase in oxyhaemoglobin - HbO2 [red] HbO2 is diamagnetic If HbO2 increases then T2 relaxation gets longer and the MRI signal increases fMRI uses a BOLD [Blood Oxygen Level Dependent] MRI pulse sequence

functional MRI of motor function Paradigm: * stimulus every 12 seconds * if ‘2’ press; if ‘5’ don’t press

Anticipation Hedonia Goalmouth vs open play Goal vs Miss Anterior cinulate Inferior frontal cortx Anticipation Goalmouth vs open play Hedonia Goal vs Miss Inferior putamen & amygdala Lateral temporal cortex

Diffusion imaging A Einstein. Investigation of the theory of Brownian motion: Dover; New York, 1956

MRI: diffusion imaging Isotropic diffusion Examples: Glass of water; cerebral grey matter Anisotropic diffusion Examples: textile fibres, nerve fibres

MRI diffusion imaging

Emission tomography

In-vivo molecular imaging The purpose of molecular imaging is to improve understanding of biology and medicine through non-invasive in vivo investigation of cellular molecular events involved in normal and pathologic processes. The technologies range from experimental optical fluorescence imaging to clinical PET and SPECT SPECT SPECT PET

In emission tomography a tracer in injected intravenously and delivered by blood-flow to the organ of interest

Intravenus injection of radio-pharmaceutical The patient’s view Gamma ray detectors Intravenus injection of radio-pharmaceutical Duration 30-40 minutes

Positron emission tomography For more info on PET see: http://www.crump.ucla.edu/software/lpp/lpphome.html

SPECT Cameras

PET / SPECT PET SPECT

Emission Tomography Both techniques are based on detection of gamma rays emitted from the body after injection of a tracer. Positron Emission Tomography [PET] 11C or 18F Short half life Local cyclotron Good for study of drug delivery Single Photon Emission Tomography [SPECT] 99mTc or 123I Longer half life Can buy isotopes Good for study of drug action

Same scanner: different radio-pharmaceuticals What SPECT can measure Regional brain function: perfusion Dopamine D2 receptor availability Dopamine transporter function M1 muscarinic receptors Nicotinic receptors Same scanner: different radio-pharmaceuticals

SPECT imaging of blood supply in the brain The tracer 99mTc -HMPAO can measure the amount of blood that goes to each part of the brain. It is extracted from blood passing through the brain and trapped in brain cells. Uptake in neurones High flow Low flow Time injection 60 seconds

A typical SPECT perfusion scan

The AD perfusion pattern The probability that patients with memory loss and normal perfusion had Alzheimer's disease was 19 %. The probability of Alzheimer's disease with bilateral temporo-parietal defects was 82%

Frontal lobe dementia Frontal hypo-perfusion sometimes including temporal lobes Frontal lobe dementia Alzheimer’s disease Bi-lateral temporo-parietal deficits Bi-lateral frontal lobe deficits

Vascular dementia Multiple regions of focally reduced perfusion

Molecular imaging: Receptors & transporters

The dopamine neurotransmitter system Tyrosine Dopamine synthesis L-DOPA DA Pre-synaptic terminal Vesicles Glial cell Dopamine MAO-B Transporters COMT D2 Receptors Post-synaptic cell

Dopamine neurotransmitter tracers Tyrosine L-DOPA F18-Dopa DA Pre-synaptic terminal Glial cell Vesicles MAO-B COMT I123 IBZM or epidepride I123 FPCIT or ß-CIT Post-synaptic cell

Dopamine transporter imaging

Diagnosis and staging of PD and LBD Imaging diagnosis Clinical diagnosis Accuracy of Diagnosis in Presumed PD Meara J et al Age and Ageing 1999;28:99-102 . 26% of patients receiving inappropriate treatment Post-mortem data suggests figure may even be higher Even on first presentation SPECT shows loss of 50% of neurones Objective measurement of progression in assessment of therapy Normal PD: H&Y1 PD: H&Y2 PD: H&Y3

Measuring the biological effect of drug action

Molecular Imaging of drug action SPECT images of SERT binding

Measurement of drug action Modern antidepressant drugs (SSRIs) block the serotonin transporter (SERT) Pre-synaptic terminal Serotonin transporters (SERT) Serotonin reuptake inhibitor (SSRI) SPECT tracer Image available binding sites Synapse Serotonin Post-synaptic cell 43

Measurement of drug action before antidepressant after antidepressant